Four researchers from three COLife institutes have been awarded nearly €1M under the Chan Zuckerberg Initiative’s Measuring Metabolism Across Scales programme. Carlos Ribeiro at the Champalimaud Foundation (CF) and Theodore Alxandrow at the European Molecular Biology Laboratory (EMBL), together with Zita Carvalho-Santos at the Instituto de Medicina Molecular João Lobo Antunes (iMM) and Ricardo Henriques and Jorge Carvalho at the Gulbenkian Institute of Science (IGC), have garnered grants to conduct pioneering projects in the field of metabolism.
Through the provision of these two-year collaborative research grants, the Chan Zuckerberg Initiative (CZI) programme aims to accelerate cutting-edge research and technology in metabolism and metabolic physiology. The objective of these grants is to map, measure, and integrate metabolism across different scales—from molecules and organelles to cells and tissues—deepening our understanding of human biology, and to investigate the metabolic processes that maintain physiological homeostasis.
The research conducted by these scientists will not only expand the scientific knowledge base but also pave the way for future research initiatives that could ultimately inform treatments and cures for a wide range of diseases. Listed below is more information about the awardees and their projects.
- Zita Carvalho-Santos (iMM), Ricardo Henriques (IGC) & Jorge Carvalho (IGC)
Sub-cellular Metabolic Compartmentalization during Oocyte Development
Zita Carvalho-Santos, group leader at the Instituto de Medicina Molecular João Lobo Antunes, along with Ricardo Henriques and Jorge Carvalho, from the Instituto Gulbenkian de Ciência, will lead a project set to explore the organisation of cellular metabolism during oocyte development. This groundbreaking project holds the promise of unravelling fundamental biological phenomena and is critical for understanding how cellular metabolism impacts cellular functions in both physiological and disease settings.
“All organisms, whether bacteria, plants, fungi, or animals, are composed of the same functional units – cells. Cells are kept alive by the constant production of building blocks and energy, which result from complex transformations involving metabolic processes. Each of these processes has different metabolic requirements. How are these processes efficiently fueled? I believe the answer lies in the compartmentalization of metabolic functions” – says Zita Carvalho-Santos, when questioned about the scientific drive for this research project.
It’s likely that metabolic processes are set in specific parts of the cell for a higher efficiency of cellular processes. This effect is particularly relevant in larger cells, with the largest cell in the animal body being the oocyte, the focus of this research. The details of which metabolic processes are localised in which parts of the cell, how this spatial distribution is regulated, and what functional significance it holds, remain far from fully understood.
“This project encompasses an interdisciplinary approach and know-how in cell biology, biochemistry, advanced microscopy, microfluidics, and computational science. It will contribute to understanding metabolism across scales by mapping the spatial and temporal impact on cellular processes of the metabolon-cytoskeleton dynamics during the exciting process of oogenesis”, adds Jorge Carvalho, also a winning team member, on the methodology and multidisciplinarity of the project.
To Ricardo Henriques, “Being a part of this collaborative project is truly exciting for me as it opens up new avenues for developing groundbreaking technologies to help researchers see the inner workings of cells with better clarity. Our team specialises in advanced microscopy techniques that can capture high-resolution pictures of the molecules and structures within cells. By deploying these cutting-edge techniques in this project, we aim to create a detailed map of the location of metabolic enzymes within oocyte cells. The potential of these technologies to be adapted by other scientists for studying biological systems and processes inside cells is immense”.
And looking to the future, Henriques adds he is “thrilled to see how these new methods for capturing metabolism at the molecular level will pave the way for many exciting scientific discoveries in the future”.
BIO:
Zita Carvalho-Santos, group leader at Instituto de Medicina Molecular in Portugal, is a cell Biologist specialised in metabolism of the female germline. Zita graduated in Genetics and Microbiology in the Faculty of Sciences of the University of Lisbon. She obtained her PhD in 2010 from the Instituto Gulbenkian de Ciência, while working in the laboratory of Mónica Dias. After working in the laboratory of Carlos Ribeiro as a postdoctoral researcher, in the Champalimaud Foundation, she set up her own research lab at iMM in 2023 supported by an ERC Starting Grant from the European Research Council.
Ricardo Henriques graduated in Particle Physics and fell in love early on with Biology. He obtained his PhD while working in the laboratories led by Musa Mhlanga and Christophe Zimmer, simultaneously developing Portugal (iMM), France (Institut Pasteur), South Africa (CSIR), the UK, and the USA (Andor Technology). During this path, he started working in super-resolution microscopy and developed technologies capable of reading images of cells and viral structures. In 2013, he established his first research group at University College London (UCL); in 2017, he accepted the invitation to set up a second laboratory at the Francis Crick Institute, and in 2019, he became a professor at UCL. He arrived at Instituto Gulbenkian de Ciência in September 2020 to lead a new research group that will develop new technologies to allow us to see the invisible, like the biology of viral infection. In the same year, Ricardo was awarded an ERC Consolidator Grant to develop a new type of self-driving microscope controlled by artificial intelligence.
Jorge Carvalho has cross-disciplinary experience in bioengineering, chemistry, biophysics, and materials science. He has participated in developing miniaturised and microfluidics technologies with environmental, industry, and health applications. At the beginning of his research career, he worked in biocatalysis at Lund University in the laboratory of Prof. Rajni-Hatti Kaul, economically optimising the amidation of olein fatty acid using different enzyme reactors. During his PhD within the MIT-Portugal doctoral program, he designed and fabricated different impedance biosensors integrated with milli- and microfluidics for the characterization of biomolecular interactions kinetics and viscoelasticity while working in the labs of Prof. Guilherme Ferreira (University of Algarve), Prof. Joaquim Sampaio Cabral (IST@University of Lisbon) and Prof. Andrew Cleland (University of California – Santa Barbara). More recently and already at IGC, he implemented a method for manipulating cellular content for biophysical and mechanobiology studies while working in the research lab of Ivo Andreas Telly. Here, he focused on understanding the physical principles behind intracellular organisation. In December 2020, he became responsible for setting up the new Bioengineering Microfabrication core facility at Gulbenkian Science Institute.
- Theodore Alxandrow (EMBL) & Carlos Ribeiro (CF)
Mapping fatty acid synthesis in an entire organism, in space and time
In collaboration with Theodore Alxandrow at EMBL, Carlos Ribeiro, a Principal Investigator at the CF, is spearheading a project that aims to revolutionise our understanding of fatty acid metabolism in animals and how it responds to biological and environmental changes.
The research will employ a novel spatial metabolomics approach to generate atlases that visually represent changes in fatty acid metabolism within whole animals. This could provide unprecedented insights into the role of metabolic organisation in maintaining homeostasis, the body’s internal equilibrium. “The ability to see where fatty acid metabolism changes in a whole animal is what excites me the most”, says Ribeiro. “This knowledge would give us a deeper understanding of how environmental factors, such as climate change, affect the metabolism of insects, which are crucial for global homeostasis and human well-being”.
The key challenge is to pinpoint exactly where metabolic changes occur within an organism. Current technologies allow researchers to identify how metabolites change in response to dietary, microbiome, or environmental modifications, but they fall short in revealing the locations of these changes. “The method we will develop and validate and use in flies will allow us to overcome this challenge”, Ribeiro notes.
By unveiling the spatial organisation of fatty acid metabolism, the project would fill an important gap in our current understanding of how environmental, lifestyle, and pathological conditions impact metabolic homeostasis. This, in turn, could offer more comprehensive insights into health and diseases, particularly those conditions where metabolic dysregulation plays a pivotal role. Furthermore, environmental fluctuations, including temperature variations, can also affect insect homeostasis, thereby potentially exacerbating the impact of climate change.
The project unites Theodore Alxandrow’s EMBL laboratory, specialised in the development of spatial metabolomics technologies, with Carlos Ribeiro’s laboratory, which possesses extensive expertise in investigating the effects of diet, microbiome, and environmental changes on whole-animal metabolism. According to Ribeiro, “Pairing technological expertise with ambitious biological questions is the best way to break new grounds”.
BIO:
Carlos Ribeiro, a founding Group Leader in the CF’s neuroscience programme, was born to immigrant parents in Switzerland. He earned his PhD from the University of Basel’s Biozentrum, where he pioneered 3D live time-lapse confocal imaging to study Drosophila embryo development. As an EMBO Postdoctoral fellow at the Research Institute of Molecular Pathology (IMP) in Vienna, he initiated a groundbreaking research programme on brain-body interactions and behaviour shaped by reproductive and nutrient states. Ribeiro was instrumental in advancing the study of behavioural nutrient homeostasis in Drosophila, demonstrating how flies adjust their nutrient preferences based on internal states.
His interdisciplinary work, bridging behaviour, neuroscience, metabolism, and the microbiome, has unveiled conserved mechanisms governing food choices and their impact on life-history traits. His lab at the CF has also innovated technologies like flyPAD and optoPAD, positioning Drosophila as a key model for studying nutritional homeostasis and physiology. He has taken on broader international leadership roles and is currently Secretary General of the Federation of European Neuroscience Societies and a member of EMBO.
About the Chan Zuckerberg Initiative
The Chan Zuckerberg Initiative was founded in 2015 to help solve some of society’s toughest challenges — from eradicating disease and improving education, to addressing the needs of our local communities. Our mission is to build a more inclusive, just, and healthy future for everyone. For more information, please visit chanzuckerberg.com.